effect of md1003 in amyotrophic lateral sclerosis

Conditions: ALS; Amyotrophic Lateral Sclerosis; Motor Neuron Disease

Summary: this is a 6-month double blind randomized 2:1 placebo-controlled study with two arms (placebo, biotin 300 mg/day). the study will be followed by a 6-month extension phase during which all patients will receive biotin 300 mg/day.


Eligibility criteria:
inclusion criteria: * age: 25 to 80 years, inclusive * male or female subjects with probable or confirmed als (revised international el escorial criteria, forbes et al., 2001). * patients presenting first motor deficits due to als for a maximum of three years at the first consultation in an als centre. * patients monitored for at least 6 months in an als centre or for whom the previous monitoring parameters are available (excepted for mip and snip). * patients who have lost at least 5 points on the alsfrs-r (als functional rating scale) during the last 12 months or at least 2 points during the preceding 6 months * patients who have been treated with riluzole for at least 3 months at a stable dose. in case of intolerance to this product or refusal for this treatment, patients who have not been treated with riluzole for at least 1 month before inclusion * for patients with spinal form (onset of the disease affecting limbs) or respiratory form, slow vital capacity \> 60% of predicted value. * for patients with a bulbar form, slow vital capacity \> 60% of theoretical value or, if spirometry not assessable (severe bulbar disability), patient should not have significant abnormality in both nocturnal capnography and nocturnal oximetry (median pco2 (carbon dioxide partial pressure ) \< 52 mmhg, sao2 (arterial oxygen saturation ) \< 90% less than 5% of the time during night) less than 3 months prior inclusion. * patients who are willing to give written consent (or oral consent in the presence of a trusted person if the patient is no longer able to write) * patients likely to be able to participate in all scheduled evaluation and complete all required study procedures (except for spirometry in bulbar patients with severe disability). exclusion criteria: * patients on non-invasive ventilation for respiratory insufficiency due to als for more than 10 hours a day * patients with an alsfrs-r score at inclusion of \< 20 (maximum score without disability = 48) * patients who have lost less than 5 points on the alsfrs-r during the last year or less than 2 points during the preceding 6 months * patients with a gastrostomy * patients who have lost more than 15% of their reference weight (defined as weight before disease onset) * patient with dyspnoea at rest or with the least effort (score \< 3 on the dyspnoea item of the alsfrs-r) * patients with dementia * patient with severe or rapidly progressive form of als for whom the investigator estimates the life expectancy less than 3 months * patients with another progressive disease that has not been stabilized at the time of inclusion * patients with cancer, except basal cell carcinoma, for less than 5 years, or who require continuous treatment for cancer even if it is older * pregnant women. * subject who are not covered by a social security scheme. * subject under temporary or permanent judicial protection. * contraception: both male subjects, and female subjects who are not either surgically sterile (tubal ligation/obstruction or removal of ovaries or uterus) or post-menopausal (no spontaneous menstrual periods for at least one year confirmed by a negative hormone panel), must commit to using two highly effective method of birth control for the duration of the study and for two months after the treatment termination.

Keywords: biotin md1003 alsfrs-r